Gene expression changes associated with chemically induced rat mammary carcinogenesis

Abstract

Experimentally induced models of breast carcinogenesis in the rat are widely used for studying the biology of breast cancer and for developing and evaluating cancer prevention and control strategies. However, very little is known about gene expression changes that are associated with experimentally induced mammary carcinogenesis. This paper reports the identification, by differential display of mRNA and molecular cloning, of seven cDNA fragments of gene transcripts overexpressed in mammary carcinomas induced by 1-methyl-1nitrosourea. These genes included the rat homologues of human galectin-7 gene, the human/mouse melanoma inhibitory activity/bovine chondrocyte-derived retinoic acid sensitive protein gene, the mouse stearoyl-CoA desaturase-2 gene, and the mouse endo B cytokeratin/human cytokeratin-18 gene. Although each of these genes has been implicated in some aspect of carcinogenesis in other organs, this paper is the first report of their overexpression in chemically induced mammary carcinomas. Two previously uncharacterized gene transcripts were also identified. A comparison of the expression levels of several genes in mammary carcinomas with those in the normal mammary gland tissue of virgin rats, mid-stage pregnant rats, and of day 1 postpartum lactating dams indicated that the overexpression of several genes observed in mammary carcinomas could not be accounted for by either a difference in the mammary epithelial content between mammary carcinoma and normal mammary tissue or by mammary epithelium-specific proliferation associated with pregnancy. Several genes were also overexpressed in rat mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene but not in azoxymethane-induced rat colon adenocarcinomas. The genes identified in this study may therefore represent mammary carcinoma-specific molecular markers that may be helpful in investigations of mammary carcinogenesis and its prevention.

Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas

“…However, PPARγ overexpression in mouse liver enhances SCD1 expression (10), while PPARγ deficiency reduces it (36). Several treatments or conditions that are associated with hepatocarcinogenesis (57, 59) also increase SCD1 expression, and SCD1 levels are higher in rat mammary carcinomas (60) and in mice that are genetically susceptible to hepatocarcinogenesis (61). Sterculic acid, an inhibitor of SCD1 activity, blocks rat mammary carcinogenesis (62).…”

Biomarkers of dietary fatty acid intake and the risk of breast cancer: A meta‐analysis

“…Overexpression of this enzyme and consequently high levels of oleic acid has been shown to be required for tumor development in experimental animal studies. [41][42][43] ⌬9-d activity is modulated by several dietary factors: saturated fatty acids, cholesterol and carbohydrates stimulate this enzyme, whereas dietary polyunsaturated fatty acids and fasting are depressors. 37 Individual animal 3 and epidemiological studies 44 -45 have generally shown that olive oil has either no effect or a protective effect on breast cancer risk, which were initially attributed to its high content of the monounsaturated fatty acid, oleic acid.…”

Upregulation of galectin-7 in murine lymphoma cells is associated with progression toward an aggressive phenotype

“…44,45 The role of galectin-7 in cancer has previously been implied in a rat model of chemically induced mammary carcinoma. 22 Galectin-7 was originally identified in the human epidermis and later found to be expressed in all types of stratified epithelial cells in the skin, tongue, esophagus, and Hassal's corpuscles in the thymus. 20,21,25 In skin keratinocytes, its expression is rapidly induced following exposure to UV irradiation in association with p53 stabilization, and an increased level of the protein was mainly found in sunburned apoptotic keratinocytes.…”

“…Among those genes whose expression were significantly altered, we further investigated the unexpected and strongly upregulated galectin-7. This gene, originally identified as a keratinocyte marker, 20,21 has previously been associated with the development of chemically induced mammary carcinoma 22 and is one of the 14 genes previously shown to be under the control of p53. 23 …”